Prostatic nuclear protein kinases active towards non-histone proteins and nuclear matrix proteins have been established by us as the androgen-regulated gene products which demonstrate a primary response to the androgenic status of the animal and correlate with the androgen receptor levels. We have purified two such cAMP-independent protein kinases (N1 and N2); the specific activity of the highly purified enzymes was 150,000 to 250,000 32P nmol/mg protein/hour. Both of the enzymes phosphorylated phosvitin or casein, but only N2 was active towards non-histone proteins. We are currently raising antibodies against the two enzymes. The availability of these antibodies should facilitate studies of the molecular biological control of these protein kinases in relation to early androgen action. We have also isolated highly purified preparations of rat ventral prostate androgen receptor; preliminary studies indicate that it may be phosphorylated by the androgen-sensitive nuclear-associated protein kinase(s). One of our goals has been to examine the nuclear proteins and protein kinases of human prostatic chromatin to identify features which might differ in the neoplastic prostate as compared with the normal. We have completed a study of the general properties of the human normal and benign hypertrophic prostate (BPH) chromatin-associated protein kinase reactions. There was no change in the activity of the BPH chromatin as compared with the normal prostate chromatin when tested with phosvitin or lysine-rich histone as substrate. However, a marked increase (by 150%) was found in the rate of phosphorylation of endogenous chromatin-associated, non-histone proteins in BPH chromatin as compared with the normal. The underlying mechanism of this observation and also similar studies of the chromatin from prostatic carcinoma are in progress. (N)